In the United States, about 2 billion dollars are spent each year on orthopedic and dental implants. This correlates to about 700,000 orthopedic implant procedures performed in one year alone. As for dental implant procedures, about 69 percent of adults aged 35-44 years have lost at least one permanent tooth and, as such, are candidates for dental implants.
An implant, be it dental, orthopedic or other, is usually a biologically compatible material, like titanium, which is surgically inserted within the body to replace defective structures such as bone or teeth. Although these implants are becoming more commonplace, problems still remain in the area of osseointegration, both immediate and long-term. Most implant procedures focus mainly on mechanical repair without much thought as to regeneration of bone. It has been shown that the replacement of bones such as hip joints that initially osseointegrate properly deteriorate years later because of osteolysis at the bone to implant interface.
In order to lengthen the lifetime of implants and to accelerate the bone healing process, some research focuses on improving the initial anchorage of the implant as well as on preserving the strength of the bone to implant interface. However, none of these current approaches are satisfactory.
Transforming growth factor-β3 is a member of a superfamily of cell mediators and plays fundamental roles in the regulation of cell proliferation and differentiation. In wound healing, TGFβ3 has been reported to attenuate type I collagen synthesis and reduce scar tissue formation. TGFβ3 has been reported to regulate the ossification of fibrous tissue in cranial sutures in craniosynostosis, a congenital disorder affecting 1 in approximately 2,500 live human births and manifesting as skull deformities, blindness, mental retardation, and death. During development, TGFβ3 regulates the adhesion of epithelial cells and subsequent fusion of the two palatal shelves, the failure of which leads to cleft palate. During umbilical cord development, TGFβ3 downregulation results in the commonly observed abnormal structure and mechanical properties of pre-eclampsia in umbilical cords, a leading cause of maternal and infant death during umbilical cord formation. TGFβ3 mediates the proliferation of corneal stromal fibroblasts by activating other endogenous factors, including FGF-2. The mechanism of fibrosis after glaucoma surgery is mediated by TGFβ3 and its effects on subconjunctival fibroblasts.
The fundamental roles of TGFβ3 in the development of a wide range of cells and tissues have prompted its adoption in tissue repair approaches. Topical application of TGFβ3 in gels was reported to ameliorate wound healing in patients at a dose of 2.5 μg/cm compared to placebo gels. Collagen gels soaked with TGFβ3 delivered to the ossifying cranial suture have been reported to delay its premature fusion. Bioactive TGFβ3 released from PLA microgrooved surfaces was reported to inhibit the proliferation of lung epithelial cells up to 24 hrs. Previous attempts for controlled release of cytokines include lipid nanoparticles, chitosan or gelatin-based particles collagen ceramics and porous glass. Although the short-term bioactivity of TGFβ3 has been investigated, exploration of prolonged release via microencapsulation is necessary for widespread needs to regulate cellular activities in the long-term during wound healing and tissue regeneration.
Despite previous efforts to investigate the therapeutic potential of TGFβ3, its effective use is limited by a number of common shortcomings such as short half life, instability in vivo, and relative inaccuracy of delivery systems.